The ability of the pulmonary alveolar epithelium to actively transport ions and water is vital to the maintenance of normal lung function. During fetal life this ability is necessary for normal lung development, it is important in the preparation for the transition to air-breathing life, and it probably plays a vital role in maintaining the thin alveolar fluid lining in mature, air- filled lungs. Defects in this system almost certainly contribute to cystic fibrosis, neonatal respiratory distress syndrome and pulmonary edema. The overall goal of this project is to determine the source of alveolar liquid and understand its role in lungs. The specific goals include: 1. In newborn lambs, measure the decrease in alveolar chloride concentration during the first few minutes following lung inflation. 2. Measure the effect of Na+ channel blockade on the decrease in alveolar chloride at birth in newborn lambs. 3. Measure the effects of Na+ blockade on clearance and distribution of lung water in newborn rabbit pups. 4. Evaluate the transport of some organic anions across the alveolar epithelium in chronically catheterized fetal lambs. 5. Confirm previous measurements of alveolar subphase composition in mature rabbits by a second method. 6. Evaluate the control of pH of the alveolar subphase. 7. Look for evidence of Na+/glucose cotransport across the alveolar epithelium. 8. Measure the effects of ion transport promoters and inhibitors on the transepithelial potential difference. For all but objectives 3 and 4 the measurements are made by puncturing the alveoli of anesthetized, newborn lambs or mature rabbits with ion selective and non-selective microelectrodes. Experimental conditions are set in each experiment according to the goal pursued. For objective 3 changes in lung water content and distribution are measured in newborn rabbits which have inhaled amiloride with their first breath. For objective 4 concentration of various organic anions added to the lung are measured by HPLC in samples of serum and fetal lung fluid.